RESUMO
Buprenorphine hydrochloride (Bup-HCl) is a common injectable opioid analgesic. In ferrets, Bup-HCl must be administered every 8 to 12 h to maintain clinical efficacy. Extended-release analgesics offer multiple advantages, including reduced handling and injection frequency, improved compliance, and increased protection from end-of-dose failure. Although efficacy of extended-release buprenorphine formulations has been demonstrated in other species, their use in the domestic ferret has not been investigated. In this study, we evaluated the pharmacokinetics of a compounded polymeric formulation of buprenorphine (Bup-ER) and a pharmaceutical-grade, FDA-indexed liposomal suspension (Bup-XR). Two doses each of Bup-ER (0.12 and 0.2 mg/kg) and Bup-XR (0.2 and 0.6 mg/kg SC) were administered to young adult female ferrets and plasma concentrations were measured between 0 and 96 h (n = 4 animals per timepoint). All doses of both drugs achieved therapeutic plasma levels by 30 min. Furthermore, high-dose Bup-XR maintained therapeutic levels for 72 h, followed by high-dose Bup-ER (less than 48 h), low-dose Bup-XR (24 h), and low-dose Bup-ER (less than 24 h). In this study, we also developed a pain scoring system and utilized this to compare analgesic efficacy between single high-dose Bup-XR (0.6 mg/kg SC) and a standard postoperative course of Bup-HCl (0.02 mg/kg SC every 10 to 12 h for 8 doses) after ovariohysterectomy. Ferrets receiving Bup-XR had significantly lower respiratory rate and posture scores in the first 24 h postoperatively than did those that received Bup-HCl and were less likely to react to palpation of the surgical incision. Of note, ferrets that received high-dose Bup-ER had a significantly higher incidence of injection site reactions than ferrets that received Bup-HCl (P = 0.0137). This study demonstrates that a single dose of Bup-XR (0.6 mg/kg SC) is a safe and effective analgesic in female ferrets, with a duration of action up to 72 h and minimal side effects, offering a refinement to analgesia in this species.
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Extracellular vesicles (EVs) can be loaded with therapeutic cargo and engineered for retention by specific body sites; therefore, they have great potential for targeted delivery of biomolecules to treat diseases. However, the pharmacokinetics and biodistribution of EVs in large animals remain relatively unknown, especially in primates. We recently reported that when cell culture-derived EVs are administered intravenously to Macaca nemestrina (pig-tailed macaques), they differentially associate with specific subsets of peripheral blood mononuclear cells (PBMCs). More than 60% of CD20+ B cells were observed to associate with EVs for up to 1 h post-intravenous administration. To investigate these associations further, we developed an ex vivo model of whole blood collected from healthy pig-tailed macaques. Using this ex vivo system, we found that labelled EVs preferentially associate with B cells in whole blood at levels similar to those detected in vivo. This study demonstrates that ex vivo blood can be used to study EV-blood cell interactions.
Assuntos
Vesículas Extracelulares , Animais , Vesículas Extracelulares/metabolismo , Leucócitos Mononucleares , Distribuição Tecidual , Macaca nemestrina , Comunicação CelularRESUMO
The domestic ferret (Mustela putorius furo) is a common research model for infectious disease and behavioral studies. Ferrets are social animals that are commonly pair-housed. The United States has no species-specific regulatory standards for housing ferrets. Optimal enclosure dimensions have also not been investigated in this species, and cage sizes reported in the literature vary. Adequate space is an important animal welfare consideration, as smaller cages have been linked to increased incidence of stress- or boredom-related behaviors in some species. Here, we evaluated activity budget and space utilization in 2 different enclosure sizes for pair-housed female ferrets (n = 12). Single cages measured 78.7×78.7×45.7cm; double cages were comprised of 2 single cages connected by a short tunnel measuring 17.8 cm. Three pairs of ferrets were housed in each cage size and continuous video recordings were captured for 2 wk prior to crossover to the other cage size. The overall activity budget was similar between groups, with the predominant behavior being inactivity (89%). Stereotypic behaviors, such as cage biting or escape attempts, were infrequent (<0.1%) in both groups. Ferrets in double cages remained in the same cage as their partner 96% of the time, suggesting that social support is very valuable. Our results suggest that ferrets in both cage sizes experienced satisfactory welfare conditions. Our findings also suggest that while cage size is not the only determinant of conspecific aggression, larger cages may be an effective intervention to ameliorate aggression in certain ferrets based on signalment or behavioral history, with particular utility as a potential alternative to re-pairing or single-housing. This study provides valuable information to guide animal care and use programs regarding appropriate ferret housing.
Assuntos
Furões , Habitação , Animais , Feminino , Estados Unidos , Bem-Estar do Animal , Comportamento Estereotipado , Criação de Animais DomésticosRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has evolved into multiple variants. Animal models are important to understand variant pathogenesis, particularly for variants with mutations that have significant phenotypic or epidemiological effects. Here, cohorts of naive or previously infected Syrian hamsters (Mesocricetus auratus) were infected with variants to investigate viral pathogenesis and disease protection. Naive hamsters infected with SARS-CoV-2 variants had consistent clinical outcomes, tissue viral titers, and pathology, while hamsters that recovered from initial infection and were reinfected demonstrated less severe clinical disease and lung pathology than their naive counterparts. Males had more frequent clinical signs than females in most variant groups, but few sex variations in tissue viral titers and lung pathology were observed. These findings support the use of Syrian hamsters as a SARS-CoV-2 model and highlight the importance of considering sex differences when using this species. IMPORTANCE With the continued circulation and emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, understanding differences in the effects between the initial infection and a subsequent reinfection on disease pathogenesis is critical and highly relevant. This study characterizes Syrian hamsters as an animal model to study reinfection with SARS-CoV-2. Previous infection reduced the disease severity of reinfection with different SARS-CoV-2 variants.
Assuntos
COVID-19 , SARS-CoV-2 , Cricetinae , Animais , Feminino , Humanos , Masculino , Mesocricetus , SARS-CoV-2/genética , COVID-19/patologia , Pulmão/patologia , Reinfecção/patologia , Modelos Animais de DoençasRESUMO
Central venous catheters (CVCs) are invaluable devices in large animal research as they facilitate a wide range of medical applications, including blood monitoring and reliable intravenous fluid and drug administration. Specifically, the tunneled multi-lumen Hickman catheter (HC) is commonly used in swine models due to its lower extrication and complication rates. Despite fewer complications relative to other CVCs, HC-related morbidity presents a significant challenge, as it can significantly delay or otherwise negatively impact ongoing studies. The proper insertion and maintenance of HCs is paramount in preventing these complications, but there is no consensus on best practices. The purpose of this protocol is to comprehensively describe an approach for the insertion and maintenance of a tunneled HC in swine that mitigates HC-related complications and morbidity. The use of these techniques in >100 swine has resulted in complication-free patent lines up to 8 months and no catheter-related mortality or infection of the ventral surgical site. This protocol offers a method to optimize the lifespan of the HC and guidance for approaching issues during use.
Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Animais , Suínos , Cateteres Venosos Centrais/efeitos adversos , Cateteres de DemoraRESUMO
An 11-year-old male common marmoset (Callithrix jacchus) presented with chronic, progressive weight loss and diarrhoea. Response to treatment with nutritional supplementation, antibiotics and immunosuppressants was modest and transient, and the animal was humanely euthanized. At necropsy, the proximal 8 cm of small intestine was diffusely pale with transmural thickening. The lungs contained coalescing tan, firm nodules measuring up to 4 mm in diameter. Histological examination revealed infiltrative mucinous adenocarcinoma of the duodenum with extensive metastases to the lungs, liver and left parapatellar adipose tissue. The mucinous matrix secreted by the primary and metastatic lesions was strongly periodic acid-Schiff positive. Warthin Starry staining for spirochaetes was negative. Pancytokeratin expression was attenuated in the primary tumour as well as in the metastases, which correlated to a poorly differentiated phenotype. To the authors' knowledge, this is the first report of a proximal duodenal adenocarcinoma with extensive metastatic disease in a common marmoset.